Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease.

Lipid nanoparticles (LNPs) represent the forefront of mRNA delivery platforms, yet achieving precise delivery to specific cells remains a challenge. The current targeting strategies complicate the formulation and impede the regulatory approval process. Here, through a straightforward regulation of helper lipids within LNPs, we introduce an engineered LNP designed for targeted delivery of mRNA into hepatocytes for metabolic dysfunction-associated fatty liver disease (MAFLD) treatment. The optimized LNP, supplied with POPC as the helper lipid, exhibits a 2.49-fold increase in mRNA transfection efficiency in hepatocytes compared to that of FDA-approved LNPs. CTP:phosphocholine cytidylyltransferase α mRNA is selected for delivery to hepatocytes through the optimized LNP system for self-calibration of phosphatidylcholine levels to prevent lipid droplet expansion in MAFLD. This strategy effectively regulates lipid homeostasis, while demonstrating proven biosafety. Our results present a mRNA therapy for MAFLD and open a new avenue for discovering potent lipids enabling mRNA delivery to specific cells.

Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.

Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery.

The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference for mRNA delivery into the spleen with exceptional transfection efficiency. We optimized IMIL structures by constructing and screening a multidimensional IMIL library containing multiple heads, tails, and linkers to perform a structure-activity correlation analysis. Following high-throughput in vivo screening, we identified A3B7C2 as a top-performing IMIL in spleen-specific mRNA delivery via the formulated LNPs, achieving a remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent in splenic dendritic cell transfection. Comparative analyses revealed that A3B7C2-based LNPs achieved a notable 2.8-fold and 12.9-fold increase in splenic mRNA transfection compared to SM102 and DLin-MC3-DMA lipid formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement in splenic mRNA expression compared to the SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues for further research in spleen-selective mRNA delivery. This work offers valuable insights for the swift discovery and rational design of ionizable lipid candidates tailored for spleen-selective transfection, thereby facilitating the application of mRNA therapeutics in spleen-related interventions.

Global, regional and national burdens of depression in adolescents and young adults aged 10-24 years, from 1990 to 2019: findings from the 2019 Global Burden of Disease study.

BACKGROUND: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time. AIMS: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years. METHOD: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019. RESULTS: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males. CONCLUSIONS: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

Detection and elimination of trace d-lactic acid in lignocellulose biorefining chain: Generation, flow, and impact on chiral lactide synthesis.

High chiral purity of lactic acid is a crucial indicator for the synthesis of chiral lactide as the primary intermediate chemical for ring-open polymerization of high molecular weight polylactic acid (PLA). Lignocellulose biomass is the most promising carbohydrate feedstock for commercial production of PLA, but the presence of trace d-lactic acid in the biorefinery chain adversely affects the synthesis and quality of chiral lactide. This study analyzed the fingerprint of trace  d-lactic acid in the biorefinery chain and found that the major source of  d-lactic acid comes from lignocellulose feedstock. The naturally occurring lactic acid bacteria and water-soluble carbohydrates in lignocellulose feedstock provide the necessary conditions for  d-lactic acid generation. Three strategies were proposed to eliminate the generation pathway of  d-lactic acid, including reduction of moisture content, conversion of water-soluble carbohydrates to furan aldehydes in pretreatment, and conversion to  l-lactic acid by inoculating engineered  l-lactic acid bacteria. The natural reduction of lactic acid content in lignocellulose feedstock during storage was observed due to the lactate oxidase-catalyzed oxidation of  l- and  d-lactic acids. This study provided an important support for the production of cellulosic  l-lactic acid with high chiral purity.

Optimizing transseptal puncture guided by three-dimensional mapping: the role of a unipolar electrogram in a needle tip.

AIMS: A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, has been only minimally reported. Indications for 3D-TSP remain unclear. Against this background, this study aims to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS: We developed a new methodology for 3D-TSP based on a unipolar electrogram derived from a transseptal needle tip (UEGM tip) in 102 patients (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on the UEGM tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at the central FO. Changes in the COI, serving as a major criterion to establish a 3D-TSP workflow, proved to be the most valuable indicator for identifying the FO in 99% (101/102) of patients compared with three previous techniques (three minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion. A total of 99.9% (1042/1043) patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. Intracardiac echocardiography guidance was required for 6.6% (69/1042) of patients. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION: In most patients, fluoroless 3D-TSP was successfully achieved using changes in the COI on the UEGM tip. Patients who met all four criteria were considered suitable for 3D-TSP, while those who met none required ICE guidance.

Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients.

BACKGROUND: We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS: Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION: FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

BACKGROUND: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING: 38 community health centers in Xiamen, China. PATIENTS: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE: Xiamen Municipal Health Commission.

Effect of DHCR7 on adipocyte differentiation in goats.

Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro, and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis. In the process of subcutaneous preadipocytes differentiation, overexpression of DHCR7 inhibited the expression of adipocytes differentiation marker genes (CEBP/α, CEBP/ß, SREBP1 and AP2), lipid metabolism-related genes (AGPAT6, FASN, SCD1 and LPL), and the lipid accumulation. However, in intramuscular preadipocyte differentiation, DHCR7 overexpression showed a promoting effect on adipocyte differentiation marker genes (CEBP/α, CEBP/ß, PPARγ and SREBP1) and lipid metabolism-related genes (GPAM, AGPAT6, DGAT1 and SCD1) expression, and on lipid accumulation. In summary, our work demonstrated that DHCR7 played an important role in regulating adipogenic differentiation and lipid metabolism in preadipocytes in goats, which is of great significance for uncovering the underlying molecular mechanism of adipocyte differentiation and improving goat meat quality.

Emodin alleviates CRS4-induced mitochondrial damage via activation of the PGC1α signaling.

Cardiorenal syndrome type 4 (CRS4), a progressive deterioration of cardiac function secondary to chronic kidney disease (CKD), is a leading cause of death in patients with CKD. In this study, we aimed to investigate the cardioprotective effect of emodin on CRS4. C57BL/6 mice with 5/6 nephrectomy and HL-1 cells stimulated with 5% CKD mouse serum were used for in vivo and in vitro experiments. To assess the cardioprotective potential of emodin, we employed a comprehensive array of methodologies, including echocardiography, tissue staining, immunofluorescence staining, biochemical detection, flow cytometry, real-time quantitative PCR, and western blot analysis. Our results showed that emodin exerted protective effects on the function and structure of the residual kidney. Emodin also reduced pathologic changes in the cardiac morphology and function of these mice. These effects may have been related to emodin-mediated suppression of reactive oxygen species production, reduction of mitochondrial oxidative damage, and increase of oxidative metabolism via restoration of PGC1α expression and that of its target genes. In contrast, inhibition of PGC1α expression significantly reversed emodin-mediated cardioprotection in vivo. In conclusion, emodin protects the heart from 5/6 nephrectomy-induced mitochondrial damage via activation of the PGC1α signaling. The findings obtained in our study can be used to develop effective therapeutic strategies for patients with CRS4.

Child loss and depressive symptoms among Chinese older adults: The moderating role of community care service.

Child loss is recognized as a risk factor for Chinese older adults' mental health, yet the differential impact and protective factors related to this association are not fully understood. This study examines potential differences in the effects of the deceased child's gender and only-child status, as well as the moderating role of community care service. Data is collected from a sample of 9686 Chinese older adults through the 2018 China Longitudinal Aging Social Survey. The results indicate that the loss of a son has a more significant impact on depressive symptoms among Chinese older adults than the loss of a daughter. The effect of child loss on depressive symptoms is not related to being an only child. Furthermore, community care service can buffer the negative impact of child loss on depressive symptoms. This study holds significant practical implications for enhancing the mental health of bereaved older adults.

Digital transformation and environmental, social, and governance greenwashing: Evidence from China.

This paper examines the relationship between digital transformation(DT) and environmental, social, and governance(ESG) greenwashing using Chinese listed companies as a sample from 2012 to 2022. Furthermore, it analyzes the enterprise and regional heterogeneity as well as the influencing mechanisms on this relationship. The research results indicate that corporate digital transformation significantly inhibits ESG greenwashing, with a more pronounced effect on companies in non-high-pollution industries, high-tech industries, and the eastern region. In addition, mechanism tests reveal that internal control and financing constraints play a partial mediating role. Digital transformation suppresses ESG greenwashing by enhancing the quality of internal control and alleviating financing constraints. The primary contribution of this paper lies in demonstrating that digital transformation can serve as a strategic tool to mitigate ESG greenwashing. This enriches the research on the outcomes of digital transformation as well as the factors influencing ESG greenwashing. The conclusions of this paper provide theoretical foundations and policy recommendations for better ESG development by enterprises and governments in emerging markets. At the same time, this paper has a certain guiding role for the introduction and implementation of policies to encourage digital transformation.

Transient Stimulated Raman Excited Fluorescence Spectroscopy.

The pursuit of better sensitivity has always been one of the central themes in Raman spectroscopy. Recently, all-far-field single-molecule Raman spectroscopy has been demonstrated by a novel hybrid spectroscopy that couples Raman scattering with fluorescence emission. However, such frequency-domain spectroscopy lacks efficient hyperspectral excitation methods and encounters intrinsic strong fluorescence backgrounds from electronic transitions, hindering its applications in advanced Raman spectroscopy and microscopy. Here we report the ultrafast time-domain spectroscopy counterpart named transient stimulated Raman excited fluorescence (T-SREF): excited by two successive broadband femtosecond pulse pairs (i.e., the pump and Stokes pulses) with time-delay scanning, strong vibrational wave packet interference is revealed on the time-domain fluorescence trace, resulting in background-free spectra of the corresponding Raman modes after the Fourier transform. T-SREF achieves background-free Raman spectra of electronic-coupled vibrational modes with sensitivity up to the level of a few molecules, which paves the way for supermultiplexed fluorescence detection and molecular dynamics sensing.

Liver Injury Traceability: Spatiotemporally Monitoring Oxidative Stress Processes by Unit-Emitting Carbon Dots.

Exploring the etiology of liver injury is critical to fundamental science and precise treatment, which has not yet been achieved by molecule imaging techniques. Herein, we manage to conquer this challenge by spatiotemporally monitoring oxidative stress processes using the proposed unit-emitting carbon dots (UE-C-dots) as fluorescent probes. We discover and reveal that the UE-C-dots can specifically determine hypochlorous acid (HClO) molecules, one of the important reactive oxygen/nitrogen species (ROS/RNS) in liver injury, by an excited state oxidation mechanism. Other ROS/RNS do not interfere with the assay even if their concentrations are 1000 times higher than that of HClO due to the lowest unoccupied molecular orbital level mismatch. Real-time tomographic imaging demonstrates that different stimuli cause distinctly different HClO bursts in both temporal and spatial dimensionalities. Therefore, the measurement and analysis of temporal information substantially extend our understanding on the relationships of hepatic oxidative stress and corresponding physiological/pathological behaviors.

Co-production of 7-chloro-tryptophan and indole pyruvic acid based on an efficient FAD/FADH2 regeneration system.

Efficient FAD/FADH2 regeneration is vital for enzymatic biocatalysis and metabolic pathway optimization. Here, we constructed an efficient and simple FAD/FADH2 regeneration system through a combination of L-amino acid deaminase (L-AAD) and halogenase (CombiAADHa), which was applied for catalyzing the conversion of an L-amino acid to halide and an α-keto acid. For cell-free biotransformation, the optimal activity ratio of L-AAD and halogenase was set between 1:50 and 1:60. Within 6 h, 170 mg/L of 7-chloro-tryptophan (7-Cl-Trp) and 193 mg/L of indole pyruvic acid (IPA) were synthesized in the selected mono-amino acid system. For whole-cell biotransformation, 7-Cl-Trp and IPA synthesis was enhanced by 15% (from 96 to 110 mg/L) and 12% (from 115 to 129 mg/L), respectively, through expression fine-tuning and the strengthening of FAD/FADH2 supply. Finally, ultrasound treatment was applied to improve membrane permeability and adjust the activity ratio, resulting in 1.6-and 1.4-fold higher 7-Cl-Trp and IPA yields. The products were then purified. This system could also be applied to the synthesis of other halides and α-keto acids. KEY POINTS: • In this study, a whole cell FAD/FADH2 regeneration system co-expressing l-AAD and halogenase was constructed • This study found that the activity and ratio of enzyme and the concentration of cofactors had a significant effect on the catalytic process for the efficient co-production of 7-chlorotryptophan and indole pyruvate.

Mitochondrial DNA copy number in peripheral blood of IgA nephropathy: a cross-sectional study.

Mitochondrial DNA (mtDNA) copy number (CN) is a biomarker of mitochondrial function and has been reported associated with kidney disease. However, its association with IgA nephropathy (IgAN), the most common cause of glomerulonephritis (GN), has not been evaluated. We included 664 patients with biopsy-proven IgAN and measured mtDNA-CN in peripheral blood by multiplexed real-time quantitative polymerase chain reaction (RT-qPCR). We examined the associations between mtDNA-CN and clinical variables and found that patients with higher mtDNA-CN had higher estimated glomerular filtration rate (eGFR) (r = 0.1009, p = .0092) and lower serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) (r=-0.1101, -0.1023, -0.07806, respectively, all p values <.05). In terms of pathological injury, mtDNA-CN was higher in patients with less mesangial hypercellularity (p = .0385, M0 vs. M1 score by Oxford classification). Multivariable logistic regression analyses also showed that mtDNA-CN was lower for patients with moderate to severe renal impairment (defined as eGFR < 60 mL/min/1.73 m2) vs. mild renal impairment, with the odds ratio of 0.757 (95% confidence interval: 0.579-0.990, p = .042). In conclusion, mtDNA-CN was correlated with better renal function and less pathological injury in patients with IgAN, proposing that systemic mitochondrial dysfunction may be involved in or reflect the development of IgAN.

Tracking indirect water footprints, virtual water flows, and burden shifts related to inputs and supply chains for croplands: A case for maize in China.

Increasing crop yields to ensure an adequate food supply under water and land scarcity is dependent on intensive agricultural inputs (such as fertilizers, pesticides, agri-films, or energy) which consume water resources and generate water pollution. However, the burden shifting of water quantity and quality stress from producers to importer and consumers through agricultural input production, trade, and consumption have been largely overlooked. Here, taking maize in China as the study case, we mapped step-by-step indirect water footprint (IWF) of maize production, virtual water (VW) flows related to inputs driven by maize consumption, and the resulting burden shifting of water quantity and quality. Bottom-up WF accounting approach was applied. The maize consumption was intercepted into two stages: the crop production stage (CPS) from raw materials to the farm, and the crop trade stage (CTS) from farm to fork. Results show that the national average blue and grey IWF of maize production was 3.91 and 26.86 m3/t, respectively. In the CPS, the input-related VW flowed from the west and east coast to the north. In the CTS, the VW flows from the north to the south. Blue and grey VW flows in CTS caused by secondary flows of VW in CPS accounted for 48% and 18% of the total flows, respectively. In total VW flows along the maize supply chain, 63% of blue VW and 71% of grey VW net exports occurred in the north of severe water scarcity and water pollution levels. The analysis highlights the impact of the crop supply chain on water quantity and water quality in the consumption of agricultural inputs, the importance of step-by-step supply chain analysis for regional crop water conservation management, and the urgent need for integrated management of agricultural and industrial water resources.

Community-based service, psychological resilience and life satisfaction among Chinese older adults: A longitudinal study.

Previous research has suggested that community-based service is beneficial in promoting older adults' life satisfaction. However, there is limited knowledge of the mediating mechanisms that foster this relationship. Thus, the current study aims to explore the mediating role of psychological resilience in the association between community-based service and life satisfaction among older adults. Using data collected over four rounds of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), this study analyzes the responses of 1439 older adults in China. The results reveal that community-based service is positively related to life satisfaction among older adults. Furthermore, psychological resilience partially mediates this association, highlighting its potential role in promoting life satisfaction. These findings contribute to a deeper theoretical understanding of the mechanisms underlying the relationship between community-based service and older adults' life satisfaction while offering practical implications for enhancing the life satisfaction of older adults in China.

The early association of water irrigation with negative pressure wound therapy does not more efficiently reduce the depth of the alkali infiltration progress into the burn.

Water irrigation is an efficacious decontaminating method for dermis exposures to corrosive agents and hence has been widely applied to treat especially alkali burns. Nevertheless, once alkali has infiltrated the deep subcutaneous tissue, washing the tissue surface with water irrigation does not attenuate the damage progress. Therefore, significant efforts have been devoted to promising strategies aimed at removing the deeply infiltrated lye. According to a recent report, the negative pressure wound therapy (NPWT) reduces the pH value of the exudate from alkali-provoked burns thus accelerating wound healing. However, it remains to be ascertained whether or not NPWT coupled with water irrigation, that is, iNPWT, more effectively hinders the alkali injury deepening. In this study, we compared the effectiveness of an early application of water irrigation with or without NPWT in preventing the progressive deepening of the alkali burn in an animal model. Our histological examination results showed no appreciable difference in tissue injury depth, dermal retention, inflammatory cell infiltration, re-epithelization, and cellular function between iNPWT and water irrigation alone treatments. Thus, our results prove that the more expensive NPWT coupled with water irrigation does not more effectively hinder the alkali's injury deepening. Hence, iNPWT use should be more cautious in clinical practice.

Pressure does not affect fibrotic function of dermal fibroblast through an in vitro 3D hydrogel culture model.

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long-lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA-seq identified 437 differentially regulated genes after an 8-h compression intervention compared with control cells, among which 256 genes were up-regulated and 181 genes were down-regulated. Further q-PCR analysis confirmed that early growth response 1(EGR1) and c-fos were down-regulated after an 8-h compression intervention. However, the down-regulation of EGR1 and c-fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20-h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor ß1(TGF-ß1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α-SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.